02423nab a2200289 i 4500 publ6593 20180905115150.0 160608s2013 hu o 0|| zxx d 1533-4023 10.1097/FJC.0b013e3182993ae0 doi 2322814 mtmt SZTE Publicatio Repozitórium hun zxx Fekete Veronika Myocardial postconditioning is lost in vascular nitrate tolerance [elektronikus dokumentum] / Fekete Veronika 2013-09 298-303 Journal of cardiovascular pharmacology 62 No. 3 Organic nitrates play an important role in the therapy of ischemic heart disease; however, their clinical application is limited by the development of vascular nitrate tolerance. We have previously shown attenuation of the cardioprotective effect of preconditioning in vascular nitrate tolerance. Here, we studied whether the development of vascular nitrate tolerance affects the infarct size, limiting effect of ischemic postconditioning (IPost) in the myocardium, and whether the activation of survival kinases plays a role in the molecular mechanism of postconditioning in the presence or absence of vascular nitrate tolerance. Male Wistar rats were treated with nitroglycerin/vehicle for 3 days to induce vascular nitrate tolerance. On the fourth day, isolated hearts were subjected to 30-minute coronary occlusion followed by 120-minute reperfusion with or without IPost. In nontolerant hearts, postconditioning significantly decreased infarct size as compared with ischemia/reperfusion; however, postconditioning failed to decrease infarct size in hearts of nitrate tolerant rats. Phosphorylation of ERK 1/2, Akt, or endothelial nitric oxide synthetase showed no significant differences between the groups at the 10th minute of reperfusion. Vascular nitrate tolerance interferes with the infarct size limiting effect of IPost. Activation of survival kinases is not crucial in the molecular mechanism of postconditioning, which remains unaffected in nitrate tolerance. Murlasits Zsolt aut Aypar Eda aut Bencsik Péter aut Sárközy Márta aut Szénási Gábor aut Ferdinandy Péter aut Csont Tamás Bálint aut http://publicatio.bibl.u-szeged.hu/6593/1/2322814.pdf Dokumentum-elérés